RRC ID 56110
著者 Kajita T, Ariyoshi W, Okinaga T, Mitsugi S, Tominaga K, Nishihara T.
タイトル Mechanisms involved in enhancement of osteoclast formation by activin-A.
ジャーナル J Cell Biochem
Abstract Several growth factors in bone tissues are reported to be associated with osteoclastogenesis. Activin-A, a member of the transforming growth factor-β (TGF-β) family is known to be present in bone tissues and an important regulator in osteoclastogenesis with SMAD-mediated signaling being crucial for inducing osteoclast differentiation. In the present study, we examined the effect and underlying mechanisms of activin-A on osteoclast formation in vitro culture systems. Activin-A enhanced osteoclast formation in both mouse bone marrow cells and monocyte/macrophage cell line RAW 264.7 cells induced by receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL) and/or macrophage stimulating factor (M-CSF). We also found that activin-A stimulated bone resorption and actin ring formation induced by RANKL and/or M-CSF. Furthermore, activin-A enhanced RANKL-induced expression of nuclear factor of activated T cell cytoplasmic 1 (NFATc1), a key regulator of osteoclastogenesis, thereby increasing osteoclastogenesis-related marker gene expression, including tartrate-resistant acid phosphatase, osteoclast stimulatory transmembrane protein, and cathepsin K. Blockage of receptor binding by follistatin, an activing-binding protein suppressed the activin-A-mediated stimulation of NFATc1. In addition, activin-A increased RANKL-induced c-fos expression without significantly affecting the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathway. Pre-treatment of the cells with a specific inhibitor of SMAD2/3 attenuated the activin-A-induced expression of NFATc1 and co-immunoprecipitation assay revealed that treatment with activin-A increased physical interaction of phosphorylated-c-fos and phosphorylated-SMAD2 protein induced by RANKL. These results suggest that activin-A enhances RANKL-induced osteoclast formation mediated by interaction of c-fos and smad2/3.
巻・号 119(8)
ページ 6974-6985
公開日 2018-8-1
DOI 10.1002/jcb.26906
PMID 29737562
MeSH Activins / pharmacology* Animals Bone Marrow Cells / cytology Bone Marrow Cells / metabolism* Cathepsin K / metabolism Follistatin / pharmacology Macrophage Colony-Stimulating Factor / metabolism Male Mice NFATC Transcription Factors / metabolism Osteoclasts / cytology Osteoclasts / metabolism* Proto-Oncogene Proteins c-fos / biosynthesis RANK Ligand / metabolism RAW 264.7 Cells Smad2 Protein / metabolism Smad3 Protein / metabolism
IF 3.448
引用数 7
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)